Malignant solid tumors are masses of abnormal tissue that originate in organs or soft tissues that typically do not include fluid areas and cysts. Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Malignant solid tumors initially grow in the organ of their cellular origin. However, such cancers may spread to other organs through metastatic tumor growth in advanced stages of the disease.
Existing therapies of solid tumors include surgery, radiation, chemotherapy, targeted therapy using e.g., antibodies and in some cases hormone therapy. However, despite improvements in therapeutic interventions, metastasis is still a major cause of mortality in solid tumors.
Tumorigenesis and metastasis is thought to be regulated, inter alia, by tissue specific micro-RNAs (miRNAs or miRs). miRNAs are non-coding RNA molecules of about 21-22 nucleotides in length, which are endogenously expressed either ubiquitously or in a tissue-specific manner and play an important regulatory role in various cellular processes. miRNAs regulate gene expression by binding to complementary sequences in target messenger RNA (mRNA) molecules, typically in untranslated regions (UTRs) thereof, and triggering their repression. MiRNAs were observed to be important for a diverse range of biological processes such as development, differentiation, proliferation, growth, cell cycle and apoptosis.
miR-96 and miR-182 are two miRNAs which are part of a cluster of miRNAs containing miRs-183, 96 and 182. The miR-183/-96/-182 cluster is a highly conserved polycistronic miRNA cluster shown to be abnormally expressed in a variety of tumors.
Li et al. (Breast Cancer Research, 2014, 16:473) report that the miR-183/-96/-182 cluster is up-regulated in most breast cancers and increases cell proliferation and migration.
US 2011/0021607 discloses micro-RNA markers of breast cancer stem cells (BCSC), inter alia, micro-RNAs in the 183/-96/-182 cluster. Uses of the markers include use as targets for therapeutic intervention, as targets for drug development, and for diagnostic or prognostic methods relating to breast cancer and BCSC cell populations.
US 2014/0088170 discloses differentially expressed microRNA molecules for the treatment and diagnosis of cancer, particularly identification of several miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. Among others, differential expression of miR-96 and miR-182 in cancer cells compared to normal cells is disclosed.
There remains a need in the art for effective and specific compositions and methods for treating cancer and cancer metastasis, such as, for example, breast cancer.